title: Comparative molecular docking analysis of cytoplasmic dynein light chain DYNLL1 with pilin to explore the molecular mechanism of pathogenesis caused by Pseudomonas aeruginosa PAO.
abstract: Cytoplasmic dynein light chain 1 (DYNLL1) is a component of large protein complex, which is implicated in cargo transport processes, and is known to interact with many cellular and viral proteins through its short consensus motif (K/R)XTQT. Still, it remains to be explored that bacterial proteins also exhibit similar recognition sequences to make them vulnerable to host defense mechanism. We employed multiple docking protocols including AUTODOCK, PatchDock, ZDOCK, DOCK/PIERR and CLUSPRO to explore the DYNLL1 and Pilin interaction followed by molecular dynamics simulation assays. Subsequent structural comparison of the predicted binding site for DYNLL1-Pilin complex against the experimentally verified DYNLL1 binding partners was performed to cross check the residual contributions and to determine the binding mode. On the basis of in silico analysis, here we describe a novel interaction of DYNLL1 and receptor binding domain of Pilin (the main protein constituent of bacterial type IV Pili) of gram negative bacteria Pseudomonas aeruginosa (PAO), which is the third most common nosocomial pathogen associated with the life-threatening infections. Evidently, our results underscore that Pilin specific motif (KSTQD) exhibits a close structural similarity to that of Vaccinia virus polymerase, P protein Rabies and P protein Mokola viruses. We speculate that binding of DYNLL1 to Pilin may trigger an uncontrolled inflammatory response of the host immune system during P. aeruginosa chronic infections thereby opening a new pioneering area to investigate the role of DYNLL1 in gram negative bacterial infections other than viral infections. Moreover, by manifesting a strict correspondence between sequence and function, our study anticipates a novel drug target site to control the complications caused by P. aeruginosa infections.
authors.affiliation: National Center for Bioinformatics, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Samina
authors.initials: S
authors.lastname: Kausar
authors.forename: Muhammad
authors.initials: M
authors.lastname: Asif
authors.forename: Nousheen
authors.initials: N
authors.lastname: Bibi
authors.forename: Sajid
authors.initials: S
authors.lastname: Rashid
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D056445:Cytoplasmic Dyneins / Q000737:chemistry* / Q000378:metabolism; D036781:Fimbriae Proteins / Q000737:chemistry* / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D018832:Molecular Chaperones; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D011552:Pseudomonas Infections / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000737:chemistry* / Q000378:metabolism / Q000472:pathogenicity; D016415:Sequence Alignment; D040681:Structural Homology, Protein; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism; D015678:Viral Structural Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D018832:Molecular Chaperones; C103961:P phosphoprotein, Rabies virus; D010750:Phosphoproteins; D014764:Viral Proteins; D015678:Viral Structural Proteins; C074060:rpo7 protein, Vaccinia virus; D036781:Fimbriae Proteins; C427758:DYNLL1 protein, human; D056445:Cytoplasmic Dyneins